Neural crest cells are a population of multipotent, migratory cells that play a crucial role in many aspects of embryonic development. This group of cells emerges from the neural tube and then migrates out extensively to different areas of the body and participates in the formation of many body parts such as face, heart, cartilage, skin and peripheral nervous system. Our long-term goal is to dissect the mechanisms controlling neural crest formation and migration. In this proposal, we would like to investigate epigenetic regulation in neural crest development. Mutations in epigenetic genes are very likely to cause abnormal neural crest formation and or migration. First, the expression patterns of chosen epigenetic genes will be characterized. Their specific functions in effecting the neural crest cells will then be analyzed in depth using classical embryology in combination with modern molecular biology techniques. Abnormal neural crest development can lead to a variety of birth defects such as craniofacial defects like cleft lip and palate, heart septation defects, and agangliogenesis of the colon. Neural crest related developmental defects account for as much as one third of all congenital birth defects. In addition, neural crest derived cells are prone to numerous types of cancer, including neurofibromatosis, melanoma, pheochromocytoma and neuroblastoma. Our study of the normal mechanisms of neural crest development will provide important insights in figuring out the mistakes that may lead to birth defects and or cancer. PUBLIC HEALTH RELEVANCE: The neural crest cells are involved in a variety of birth defects and cancers such as cleft lip and palate, heart defects, colon disease and neuroblastoma. Neural crest related defects account for as much as one third of all congenital birth defects.